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Purpose To evaluate the feasibility, safety, and efficacy of local thrombolytic agents directly injected into occluded retinal veins in an experimental animal model. Design Experimental animal study. Methods This experimental study was performed in two phases. In phase 1, 15 enucleated porcine eyes and 8 in vivo canine eyes were used for the development of the instrumentation and surgical technique required for retinal vein cannulation with prolonged intravascular infusion. In phase 2 of this study, experimental branch retinal vein occlusion was photo-chemically created using an intravenous injection of rose bengal followed by diode laser photocoagulation in eight eyes of eight dogs. Four eyes were treated by retinal vein cannulation and an injection of tissue plasminogen activator (t-PA) using a specifically designed microcatheter, while the remaining four eyes were untreated (control group). The total amount of t-PA injected intravenously ranged from 400 to 1000 μg, infused over a period ranging from 25 to 45 minutes with a mean pressure of 40 psi, resulting in a mean injection flow rate of 0.05 ml/min. The dogs underwent clinical examination, fluorescein angiography, and histologic examination. Main outcome measures were: Achievement of prolonged intravascular infusion of t-PA, changes in fundus appearance, fluorescein angiography, and histology. Results A microcatheter instrument and a surgical technique for retinal vein cannulation with prolonged intravascular infusion were developed. Cannulation and t-PA infusion for a period of at least 30 minutes was achieved in all four treated eyes with experimental branch retinal vein occlusion. No complications were recorded in all treated eyes. One week and 1 month postoperatively, treated eyes exhibited marked decreases in retinal hemorrhages, retinal vein dilation, and tortuosity, whereas nontreated eyes exhibited persistence of these findings. Fluorescein angiography demonstrated improved circulatory flow in treated relative to nontreated eyes. Histologic analysis confirmed the presence of thrombi in nontreated eyes only. Conclusions Retinal vein cannulation with prolonged intravascular injection of t-PA is feasible and safe, and this may offer a new treatment option for retinal vein occlusion.

An electronic retinal prosthesis is under development to treat retinitis pigmentosa and age-related macular degeneration, two presently incurable diseases of the outer retina. Previous studies have established the feasibility of the retinal prosthesis. The goal of these experiments was to investigate chronic stimulation of the retina. These effects were measured by direct examination of the implant, electrophysiology of the retina, electrically elicited responses, and examination of histology post-implant. Implants were placed in 6 dogs. The implant featured an implantable stimulator and a 4/spl times/4 array of 460-micron diameter platinum disks positioned on the retina. 6 dogs were chronically stimulated at 0.05 mC/cm/sup 2/ and 0.1 mC/cm/sup 2/ for up to 60 days (10-12 hours/day). No retinal damage was evident from the stimulus. Some mechanical damage of the retina due to array misalignment was apparent in early implants, but this was minimized with improved surgical technique. Bright flash electroretinograms showed no changes in retinal function comparing pre and post implant recordings. Electrically evoked cortical responses were recorded from 1 dog showing that the functional connection between the retina and the remained. Histological analysis revealed normal retina under the array of 1 dog that had been stimulated for 25 days.